This application for a randomized trial to evaluate a health behavior intervention for reducing health risk behaviors and promoting health in adolescents with major depressive disorder (MDD) is being submitted in response to RFA-MH-06-002 inviting research on health behavior change in mental disorders modeled from HIV interventions. MDD in adolescence is a common and impairing disorder which leads to significant disability, morbidity, and mortality. Health risk behaviors are frequently comorbid with adolescent MDD, adding to the personal, social, and societal burden of the disorder. Effective interventions for reducing health risk behavior in adolescent MDD are important for preventing negative health consequences and improving both health and mental health outcomes. The proposal builds on our group's expertise in behavioral interventions for HIV prevention (Rotheram-Borus) and primary care interventions for depressed adolescents (Asarnow). We will enroll 300 adolescents with MDD identified through screening at the time of a primary care visit. Adolescents will be randomized to either 1) the health behavior intervention, or 2) usual care. The intervention targets four major areas of health risk behavior: tobacco use;alcohol and drug use;sexual activity;and obesity. Based on our prior HIV preventive interventions and our work integrating behavioral interventions for adolescent depression within primary health care services, the intervention employs a collaborative care model, with a Care Manager supporting the primary care provider and delivering a 10-session cognitive-behavioral health education intervention aimed at reducing health risk behaviors and promoting and maintaining positive health behaviors. Like successful HIV prevention programs, the intervention addresses multiple risk factors simultaneously, intervenes at multiple system levels (individual, family, organization), and emphasizes linking youth to care. Outcomes are monitored at baseline and at 6 and 12-month follow-ups. We hypothesize that adolescents randomized to the intervention, compared to adolescents in usual care, will have fewer health risk behaviors (our primary outcome) and improved secondary outcomes (depression, satisfaction with care, and quality of life/functioning). Results will provide critical guidance to the field regarding strategies for improving health and reducing health risk behaviors in adolescents with MDD.